Date of Graduation

5-2018

Document Type

Thesis

Degree Name

Master of Science in Cell & Molecular Biology (MS)

Degree Level

Graduate

Department

Cell & Molecular Biology

Advisor/Mentor

Pinto, Ines

Committee Member

Ivey, D. Mack

Second Committee Member

Sakon, Joshua

Keywords

Chromatin remodeler; Chromosome segregation; Histone; INO80

Abstract

Chromatin remodeling complexes are multi-protein complexes that regulate the dynamics of the nucleosomes in the genome. The INO80 chromatin remodeling complex participates in varied biological processes such as: transcription, DNA repair, DNA replication and chromosome integrity. It catalyzes the eviction of the H2A.Z variant histone as well as whole nucleosome eviction. This complex is comprised of 15 subunits and the contribution of each to chromosome segregations remains unknown. To evaluate the contribution of each subunit to chromosome segregation, we tested deletion mutants of the non-essential subunits for DNA content and benomyl sensitivity. Also, we assessed members of the SWR1 and NuA4 complexes which relate to the same substrate. Additionally, specific members of the complex were tested for genetic interaction with SGO1. The deletion of INO80, ARP5, ARP8, IES6 and TAF14 cause increased ploidy and increased benomyl sensitivity. Additionally, overexpression of SGO1 suppresses the benomyl sensitivity and possibly protects the cell from diploidization. Overall, specific subunits of the complex play a role in chromosome segregation and defects caused by mutants of INO80 could be alleviated by SGO1-mediated bi-orientation.

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